Antibodies to DNA are a prominent serological feature of systemic lupus erythematosus (SLE) and constitute a wide spectrum of specificities, including antibodies that bind only single-stranded deoxyribose nucleic acid (ssDNA), only native DNA (nDNA), and antibodies that bind both ssDNA and nDNA. Antibodies to ssDNA are not specific for SLE in comparison to anti-nDNA nDNA antibodies, which, however, occur rarely. In contrast, antibodies that bind both ssDNA and nDNA occur frequently, are relatively specific for SLE, and are associated with glomerulonephritis in some patients with SLE. There is substantial interest in determining the fine specificity of antibodies binding to nucleic acids, particularly antibodies diagnostic of SLE and lupus nephritis.